Achmatowicz reaction

To investigate the feasibility of employing 3-oxidopyridinium betaines as stabilized 1,3-dipoles in an intramolecular dipolar cycloaddition to construct the hetisine alkaloid core (Scheme 1.8, 77 78), a series of model cycloaddition substrates were prepared. In the first (Scheme 1.9a), an ene-nitrile substrate (i.e., 83) was selected as an activated dipolarophile functionality. Nitrile 66 was subjected to reduction with DIBAL-H, affording aldehyde 79 in 79 % yield. This was followed by reductive amination of aldehyde x with furfurylamine (80) to afford the furan amine 81 in 80 % yield. The ene-nitrile was then readily accessed via palladium-catalyzed cyanation of the enol triflate with KCN, 18-crown-6, and Pd(PPh3)4 in refluxing benzene to provide ene-nitrile 82 in 75 % yield. Finally, bromine-mediated aza-Achmatowicz reaction [44] of 82 then delivered oxidopyridinium betaine 83 in 65 % yield. 

SCHEME 13.118 Application of the Sharpless asymmetric aminohydroxylation and of the aza-Achmatowicz reaction to the synthesis of a l,5-dideoxy-l,5-iminoalditol. 

The synthetic utility of the present transformation is highlighted by the deriva tization of the furyl ring to form y butenolide (Scheme 3.17). As the y butenolide architecture is a common building block in the synthesis of various natural products, the F C reaction product represents a new entry to the synthetic precursors of nitrogen containing molecules. The aza Achmatowicz reaction, followed by reduc tive cyclization ofthe 1,4 dicarbonyl intermediate under Luche conditions, produced the y butenolide in good yield. 

Based on enantioselective epoxidation and subsequent ring opening and closing, the so-called Achmatowicz reaction was developed. This is an organocatalytic one-pot cascade for the annulation of a,(J-unsaturated aldehydes, hydrogen peroxide, p-carbonyl compounds and NBS, which furnish optically active 3-pyrones. Other chiral heterocycles were also assembled by organocatalytic cascade reactions using diaiylprolinol silyl ethers as catalysts. ... 

A concise sequence was developed for the total synthesis of )-6-q>i-cleistenolide (14EJO8049). It required only five steps in an overall yield of 60% from the commercially available furylallyl alcohol.The aforementioned Achmatowicz reaction took place with the furan diol intermediate to give the dihydropyranone product.The final product was obtained via a sequence of oxidation, reduction, and acetylation. 

Schreiber has developed a folding pathway which exploits the Achmatowicz reaction (Scheme 1.3). The fate of oxidation of the furan substrates 10... 

Scheme 1.3 Schreiber s approach to pre-encoding skeletal information using the Achmatowicz reaction. Reagents and conditions. (1) A -bromosuccini-mide, NaHCOj, NaOAc, THF-HjO (4 1), rt, 1 h PPTS, CH2CI2, 40-45°C, 20h, 11a 33% (64%) 11b 35% (86%) 11c 81% (>90%). Numbers in parentheses are purities determined by LC-MS.

Scheme 4.4. Use of the Achmatowicz reaction in a folding pathway for DOS by Burke et al.

The Achmatowicz reaction is based on the foregoing oxidative cleavage of the fiiran ring in furyl alcohols 49, whose oxidation is preferentially performed with tert-butyl hydroperoxide or MCPBA. The primarily formed l-hydroxy-2,5-dicarbonyl compounds 50 immediately cyclize to the corresponding pyranones 51 by intramolecular hemiacetal... 

When this oxidation-cyclization sequence is extended to furylamines 52, dihydropyri-dones with the hemiaminal structure 54 are obtained (via 53, aza-AcHMATOwicz reaction). Both product types of the Achmatowicz reaction are synthetically relevant [17]. 

Recently the total synthesis of natural (-)-sedacryptine (228) was accomplished in an organocatalyzed Mannich/ aza-Achmatowicz/A-acyliminium ion reaction sequence in 0.6% overall yield over 14 steps (Scheme 11.50) [155], Retrosynthetic analysis revealed piperidinone 223, which was accessible from sulfone 221 via asymmetric Mannich reaction, protection of the carbonyl group, and aza-Achmatowicz reaction, to be a promising intermediate toward (-)-sedacryptine (228). Then, addition of allyltri-methylsilane to the in situ formed A-acyliminium ion afforded the c -substituted piperidinone 224 as single diaste-reomer. Compound 225, which was subjected to ozonolysis. 

Aggarwal and Bi proposed the synthesis of 8a-epi-swainsonine (222) from hemiaminal 218 which was prepared from the protected amine 217 in the aza-Achmatowicz reaction as shown in Scheme 42/ The heterocyclic derivative 218 was, under the acidic conditions, transformed into the acetal the carbonyl group was then reduced, under the Luche conditions, providing derivative 219 as practically single isomer. Reduction of the double bond with simultaneous removal of the Cbz group and cleavage of the N,0-acetal afforded piperidine 220 which was easily transformed, via 221, into 8a-epi-swainsonine 222. 

Although the aza-variant of the Achmatowicz reaction is well established in the context of the synthesis of nitrogen heterocycles,its application in the field of imino sugars is still limited, especially in recent literature. However, some earlier reports can be found. ... 

---